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A Study of Combination With TBI-1401(HF10) and Ipilimumab in Japanese Patients With Unresectable or Metastatic Melanoma

Primary Purpose

Melanoma Stage III, Melanoma Stage IV

Status
Completed
Phase
Phase 2
Locations
Japan
Study Type
Interventional
Intervention
TBI-1401(HF10)
Ipilimumab
Sponsored by
Takara Bio Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Melanoma Stage III focused on measuring Unresectable melanoma, Metastatic melanoma, Recurrent Melanoma, TBI-1401(HF10), HF10, HSV-1, Oncolytic virus, Oncolytic viral immunotherapy, Ipilimumab, Intratumoral administration, canerpaturev

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients with histologically confirmed Stage IIIB, IIIC or IV unresectable or metastatic melanoma except uveal melanoma, who must have a history of treatment (chemotherapy, molecular targeted therapy, or anti PD-1 antibody therapy).
  • Patients must have measurable non-visceral lesion(s) that are evaluable by the modified World Health Organization (mWHO) criteria and immune-related response criteria (irRC).
  • Patients must be ≥ 20 years of age.
  • Patients must have a life expectancy ≥ 24 weeks.
  • Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
  • Patients must have adequate organ function, defined as

    • Total bilirubin levels ≤ 1.5 x upper limit of normal [ULN] (except for patients with Gilbert's Syndrome, who must have a total bilirubin of less than 3.0 mg/dL)
    • AST/ALT levels ≤ 2.5 x ULN, or ≤ 5 x ULN if liver metastases are present.
    • Creatinine ≤ 1.5 x ULN or creatinine clearance (calculated) ≥ 60 mL/min/1.73 m^2 for patients with creatinine > 1.5 x ULN.
    • Absolute neutrophil count ≥1,500/µL and
    • Platelet count ≥ 75,000/ µL
  • Men and women of childbearing potential must agree to use adequate contraception from the time of consent through 30 days after final study treatment.
  • Females of childbearing potential must have a negative urine or serum pregnancy test within 1 week prior to start of treatment.
  • Patients must be able to understand and willing to sign a written informed consent document.

Exclusion Criteria:

  • Patients who were previously treated with ipilimumab by intravenous infusion.
  • Patients receiving chemotherapy or molecularly targeted drug or anti-PD-1 antibody treatment or radiotherapy or immunotherapy within 4 weeks prior to initiating study treatment.
  • Patients with a history of Grade 4 adverse events caused by chemotherapy, molecularly targeted drug, anti-PD-1 antibody treatment, radiotherapy or immunotherapy conducted more than 4 weeks prior to TBI-1401(HF10) treatment, or presence of such adverse events of Grade 2 or greater, except alopecia and adverse events controlled by a treatment.
  • Patients receiving anti-herpes medication within 1 week prior to initiating TBI-1401(HF10) administration, except local treatment such as ointment.
  • Patients with a history of significant tumor bleeding, or coagulation or bleeding disorders.
  • Patients with target tumors that could potentially invade a major vascular structure (e.g., innominate artery, carotid artery), based on unequivocal imaging findings.
  • Patients with Grade 2 or greater neurologic abnormalities (CTCAE version 4.0), including Grade 2 or greater peripheral neuropathy caused by previous treatments.
  • Patients with clinically evident Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), Hepatitis C virus (HCV), or Epstein-Barr virus (EBV) infection.
  • Patients requiring systemic glucocorticoid (except 10 mg/day/body prednisolone or less) or immunosuppressive therapy because of the presence or history of autoimmune disease (e.g., Crohn's disease, ulcerative colitis) or other diseases.
  • Concurrent use of any other investigational agents within 4 weeks prior to initiating study treatment.
  • Patients with active CNS metastases or carcinomatous meningitis, except patients with CNS lesions that have been treated and have no evidence of progression in the brain on CT/MRI for ≥ 3 months.
  • Pregnant or breastfeeding women (excluding the case in which breastfeeding is discontinued and will not resume it); women desiring to become pregnant within the timeframe of the study are also excluded.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements, as determined by the investigator.

Sites / Locations

  • Clinical Site
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  • Clinical Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

TBI-1401(HF10) + Ipilimumab

Arm Description

1x10^7 TCID50/mL TBI-1401(HF10) administered to a single or multiple eligible tumors in a total volume up to 5.0 mL (injection volume will be adjusted based on the size of tumor mass) by intratumoral injection and 3 mg/kg ipilimumab administered by intravenous infusions.

Outcomes

Primary Outcome Measures

Best overall response rate (BORR) by irRC
Determine the efficacy of TBI-1401(HF10) in combination with Ipilimumab evaluated by irRC (immuno-related response criteria)

Secondary Outcome Measures

Best overall response rate (BORR) by mWHO response criteria
Determine the efficacy of TBI-1401(HF10) in combination with Ipilimumab evaluated by modified WHO (mWHO) response criteria
Best overall response rate (BORR) by RECIST version 1.1
Determine the efficacy of TBI-1401(HF10) in combination with Ipilimumab evaluated by RECIST version 1.1
Objective response rate (ORR) by irRC
Overall tumor response evaluated by irRC in the measurable target lesion(s) and unmeasurable/evaluable target lesion(s).
Objective response rate (ORR) by mWHO
Overall tumor response evaluated by mWHO response criteria in the measurable target lesion(s) and unmeasurable/evaluable target lesion(s).
Objective response rate (ORR) by RECIST version 1.1
Overall tumor response evaluated by RECIST version 1.1 in the measurable target lesion(s) and unmeasurable/evaluable target lesion(s).
Adverse event summaries, vital signs, and laboratory parameters to evaluate the safety and tolerability.
Adverse events will be evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE version 4.0).
Progression-free survival (PFS)
Evaluation the time to progression during and after the treatment.
Durable response rate (DRR)
Evaluation the length of time after a partial or complete response.
1 year survival rate
Determine the 1 year survival rate of patient who received treatment.

Full Information

First Posted
May 8, 2017
Last Updated
March 3, 2020
Sponsor
Takara Bio Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03153085
Brief Title
A Study of Combination With TBI-1401(HF10) and Ipilimumab in Japanese Patients With Unresectable or Metastatic Melanoma
Official Title
A Phase II Study of Combination Treatment With TBI-1401(HF10), a Replication-competent HSV-1 Oncolytic Virus, and Ipilimumab in Japanese Patients With Stage IIIB, IIIC, or IV Unresectable or Metastatic Malignant Melanoma
Study Type
Interventional

2. Study Status

Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
May 25, 2017 (Actual)
Primary Completion Date
June 30, 2018 (Actual)
Study Completion Date
December 14, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Takara Bio Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to determine if TBI-1401(HF10) in combination with ipilimumab is effective in Japanese patients with stages IIIB, IIIC, or IV unresectable or metastatic melanoma.
Detailed Description
The study is designed to assess efficacy and safety with repeated administration of intratumoral injections of TBI-1401(HF10) at 1x10^7 TCID50/mL in combination with intravenous infusions of 3mg/kg ipilimumab in Japanese patients. This is a single arm, open label Phase II study, to evaluate the efficacy and safety of TBI-1401(HF10) treatment in combination with the immunologic checkpoint inhibitor, ipilimumab (anti-CTLA-4 monoclonal antibody). The study population will include patients with Stage IIIB, IIIC or IV unresectable or metastatic malignant melanoma who are ipilimumab-eligible. Patients will receive the dose of 1x10^7 TCID50/mL TBI-1401(HF10) (for a total of 6 injections; the first 4 injections at 1-week intervals; the remaining 2 injections at 3-week intervals) + ipilimumab at 3 mg/kg (for a total of 4 intravenous infusions, each administered at 3-week intervals). Following combination therapy, patients may continue to receive the 1x10^7 TCID50/mL TBI-1401(HF10) alone for up to an additional 13 injections (total of 19 injections = 1 year) if they have tolerated the study treatment, are responding, have stable disease, or have progressive disease that is not clinically significant in the judgment of the Investigator.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma Stage III, Melanoma Stage IV
Keywords
Unresectable melanoma, Metastatic melanoma, Recurrent Melanoma, TBI-1401(HF10), HF10, HSV-1, Oncolytic virus, Oncolytic viral immunotherapy, Ipilimumab, Intratumoral administration, canerpaturev

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
28 (Actual)

8. Arms, Groups, and Interventions

Arm Title
TBI-1401(HF10) + Ipilimumab
Arm Type
Experimental
Arm Description
1x10^7 TCID50/mL TBI-1401(HF10) administered to a single or multiple eligible tumors in a total volume up to 5.0 mL (injection volume will be adjusted based on the size of tumor mass) by intratumoral injection and 3 mg/kg ipilimumab administered by intravenous infusions.
Intervention Type
Biological
Intervention Name(s)
TBI-1401(HF10)
Other Intervention Name(s)
HF10, canerpaturev
Intervention Description
1x10^7 TCID50/mL TBI-1401(HF10) (for a total of 6 injections; the first 4 injections at 1-week intervals; the remaining 2 injections at 3-week intervals). Following combination therapy, patients may continue to receive the 1x10^7 TCID50/mL TBI-1401(HF10) alone for up to an additional 13 injections (total of 19 injections = 1 year) if eligible for administration.
Intervention Type
Drug
Intervention Name(s)
Ipilimumab
Other Intervention Name(s)
anti CTLA-4 antibody
Intervention Description
3 mg/kg ipilimumab (for a total of 4 intravenous infusions, each administered at 3-week intervals).
Primary Outcome Measure Information:
Title
Best overall response rate (BORR) by irRC
Description
Determine the efficacy of TBI-1401(HF10) in combination with Ipilimumab evaluated by irRC (immuno-related response criteria)
Time Frame
at 24 weeks
Secondary Outcome Measure Information:
Title
Best overall response rate (BORR) by mWHO response criteria
Description
Determine the efficacy of TBI-1401(HF10) in combination with Ipilimumab evaluated by modified WHO (mWHO) response criteria
Time Frame
at weeks 24
Title
Best overall response rate (BORR) by RECIST version 1.1
Description
Determine the efficacy of TBI-1401(HF10) in combination with Ipilimumab evaluated by RECIST version 1.1
Time Frame
at weeks 24
Title
Objective response rate (ORR) by irRC
Description
Overall tumor response evaluated by irRC in the measurable target lesion(s) and unmeasurable/evaluable target lesion(s).
Time Frame
at weeks 6, 12, 18, and 24
Title
Objective response rate (ORR) by mWHO
Description
Overall tumor response evaluated by mWHO response criteria in the measurable target lesion(s) and unmeasurable/evaluable target lesion(s).
Time Frame
at weeks 6, 12, 18, and 24
Title
Objective response rate (ORR) by RECIST version 1.1
Description
Overall tumor response evaluated by RECIST version 1.1 in the measurable target lesion(s) and unmeasurable/evaluable target lesion(s).
Time Frame
at weeks 6, 12, 18, and 24
Title
Adverse event summaries, vital signs, and laboratory parameters to evaluate the safety and tolerability.
Description
Adverse events will be evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE version 4.0).
Time Frame
through study completion, up to 1 year
Title
Progression-free survival (PFS)
Description
Evaluation the time to progression during and after the treatment.
Time Frame
through disease progression, up to 3 years
Title
Durable response rate (DRR)
Description
Evaluation the length of time after a partial or complete response.
Time Frame
for 1 year
Title
1 year survival rate
Description
Determine the 1 year survival rate of patient who received treatment.
Time Frame
at 1 year
Other Pre-specified Outcome Measures:
Title
Levels of antibody to HSV-1
Description
Evaluate the change of anti-HSV-1 antibody levels.
Time Frame
up to weeks 24
Title
Change in immunologic parameters in serum
Description
Analysis the change of cytokine profiles, antitumor T-cell reactivity and regulatory T-cell (Treg) population by immunoassay and flow cytometry.
Time Frame
up to weeks 24
Title
Histopathological response with TBI-1401(HF10) administrated tumor
Description
Biopsies will be performed to evaluate the histopathological response with TBI-1401(HF10) administrated tumor.
Time Frame
up to weeks 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with histologically confirmed Stage IIIB, IIIC or IV unresectable or metastatic melanoma except uveal melanoma, who must have a history of treatment (chemotherapy, molecular targeted therapy, or anti PD-1 antibody therapy). Patients must have measurable non-visceral lesion(s) that are evaluable by the modified World Health Organization (mWHO) criteria and immune-related response criteria (irRC). Patients must be ≥ 20 years of age. Patients must have a life expectancy ≥ 24 weeks. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. Patients must have adequate organ function, defined as Total bilirubin levels ≤ 1.5 x upper limit of normal [ULN] (except for patients with Gilbert's Syndrome, who must have a total bilirubin of less than 3.0 mg/dL) AST/ALT levels ≤ 2.5 x ULN, or ≤ 5 x ULN if liver metastases are present. Creatinine ≤ 1.5 x ULN or creatinine clearance (calculated) ≥ 60 mL/min/1.73 m^2 for patients with creatinine > 1.5 x ULN. Absolute neutrophil count ≥1,500/µL and Platelet count ≥ 75,000/ µL Men and women of childbearing potential must agree to use adequate contraception from the time of consent through 30 days after final study treatment. Females of childbearing potential must have a negative urine or serum pregnancy test within 1 week prior to start of treatment. Patients must be able to understand and willing to sign a written informed consent document. Exclusion Criteria: Patients who were previously treated with ipilimumab by intravenous infusion. Patients receiving chemotherapy or molecularly targeted drug or anti-PD-1 antibody treatment or radiotherapy or immunotherapy within 4 weeks prior to initiating study treatment. Patients with a history of Grade 4 adverse events caused by chemotherapy, molecularly targeted drug, anti-PD-1 antibody treatment, radiotherapy or immunotherapy conducted more than 4 weeks prior to TBI-1401(HF10) treatment, or presence of such adverse events of Grade 2 or greater, except alopecia and adverse events controlled by a treatment. Patients receiving anti-herpes medication within 1 week prior to initiating TBI-1401(HF10) administration, except local treatment such as ointment. Patients with a history of significant tumor bleeding, or coagulation or bleeding disorders. Patients with target tumors that could potentially invade a major vascular structure (e.g., innominate artery, carotid artery), based on unequivocal imaging findings. Patients with Grade 2 or greater neurologic abnormalities (CTCAE version 4.0), including Grade 2 or greater peripheral neuropathy caused by previous treatments. Patients with clinically evident Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), Hepatitis C virus (HCV), or Epstein-Barr virus (EBV) infection. Patients requiring systemic glucocorticoid (except 10 mg/day/body prednisolone or less) or immunosuppressive therapy because of the presence or history of autoimmune disease (e.g., Crohn's disease, ulcerative colitis) or other diseases. Concurrent use of any other investigational agents within 4 weeks prior to initiating study treatment. Patients with active CNS metastases or carcinomatous meningitis, except patients with CNS lesions that have been treated and have no evidence of progression in the brain on CT/MRI for ≥ 3 months. Pregnant or breastfeeding women (excluding the case in which breastfeeding is discontinued and will not resume it); women desiring to become pregnant within the timeframe of the study are also excluded. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements, as determined by the investigator.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Naoya Yamazaki
Organizational Affiliation
National Cancer Center Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Clinical Site
City
Nagakute
State/Province
Aichi
Country
Japan
Facility Name
Clinical Site
City
Nagoya
State/Province
Aichi
Country
Japan
Facility Name
Clinical Site
City
Kurume
State/Province
Fukuoka
Country
Japan
Facility Name
Clinical Site
City
Sapporo
State/Province
Hokkaido
Country
Japan
Facility Name
Clinical Site
City
Tsukuba
State/Province
Ibaraki
Country
Japan
Facility Name
Clinical Site
City
Chūōku
State/Province
Tokyo
Country
Japan
Facility Name
Clinical Site
City
Chūō
State/Province
Yamanashi
Country
Japan
Facility Name
Clinical Site
City
Fukuoka
Country
Japan
Facility Name
Clinical Site
City
Kumamoto
Country
Japan
Facility Name
Clinical Site
City
Niigata
Country
Japan
Facility Name
Clinical Site
City
Shizuoka
Country
Japan
Facility Name
Clinical Site
City
Ōsaka
Country
Japan

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

A Study of Combination With TBI-1401(HF10) and Ipilimumab in Japanese Patients With Unresectable or Metastatic Melanoma

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